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Development of PKPD models for Hepatitis Viral Dynamics using NONMEM and Monolix software

Development of PKPD models for Hepatitis Viral Dynamics using NONMEM and Monolix software. Svetlana Vinogradova Kirill Zhudenkov Tatiana Karelina. PD model construction. DADT(3) = k_T_cell_c-k_T_cell_d*A(3)-k_inf*A(5)*A(3) DADT(4) = k_inf*A(5)*A(3)- k_I_cell_d*A(4)

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Development of PKPD models for Hepatitis Viral Dynamics using NONMEM and Monolix software

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  1. Development of PKPD models for Hepatitis Viral Dynamics using NONMEM and Monolix software Svetlana Vinogradova Kirill Zhudenkov Tatiana Karelina

  2. PD model construction DADT(3) = k_T_cell_c-k_T_cell_d*A(3)-k_inf*A(5)*A(3) DADT(4) = k_inf*A(5)*A(3)- k_I_cell_d*A(4) DADT(5) = (1-EFFICACY)*k_virus_rl*A(4) - k_virus_cl*A(5) Steady state A_0(5) is fitted k_T_cell_c = (k_I_cell_d*k_virus_cl*(V_initial+(k_T_cell_d/k_inf)))/k_virus_rl A_0(5)=V_initial PAR=k_virus_cl/k_virus_rl A_0(4)=PAR*V_initial A_0(3)=(k_I_cell_d*PAR)/k_inf

  3. Development & Final PD model

  4. Development & Final PD model We used nonparametric methods to compare parameters of the model for SVR patients with those of NR. The median EC50 didn’t differ significantly between SVR and NR groups. By contrast, the median infected cell loss rate is significantly faster in SVRs compared with NRs (0.51 vs. 0.12 days-1, P=0.029).

  5. Individual plots

  6. Individual plots

  7. Individual plots

  8. Individual plots

  9. Diagnostic plots

  10. Diagnostic plots

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